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Published on: March 28, 2017
Galeon: A Biologically Active Molecule with In Silico Metabolite Prediction, In Vitro Metabolic Profiling in Rat
A F M Motiur Rahman1, Wencui Yin1, Adnan A Kadi1
1Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Abstract:
Galeon, a natural cyclic-diarylheptanoid (CDH), which was first isolated from Myrica gale L., is known to have potent cytotoxicity against A549 cell lines, anti-tubercular activity against Mycobacterium tuberculosis H37Rv, chemo-preventive potential, and moderate topoisomerase inhibitory activity. Here, in silico metabolism and toxicity prediction of galeon by CYP450, in vitro metabolic profiling study in rat liver microsomes (RLMs), and molecular interactions of galeon-CYP450 isoforms were performed. An in silico metabolic prediction study showed demethyl and mono-hydroxy galeon were the metabolites with the highest predictability. Among the predicted metabolites, mono-hydroxy galeon was found to have plausible toxicities such as skin sensitization, thyroid toxicity, chromosome damage, and carcinogenicity. An in vitro metabolism study of galeon, incubated in RLMs, revealed eighteen Phase-I metabolites, nine methoxylamine, and three glutathione conjugates. Identification of possible metabolites and confirmation of their structures were carried out using ion-trap tandem mass spectrometry. In silico docking analysis of galeon demonstrated significant interactions with active site residues of almost all CYP450 isoforms.
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